In the study, 110 patients
received trastuzumab, 8 mg/kg
loading dose followed by 6 mg/kg
every 3 weeks, and docetaxel 100
mg/m2 every 3 weeks, while 112 received
the same trastuzumab dose, a
lower docetaxel dose (75
mg/m2), plus capecitabine 940
mg/m2 twice daily on days 1
to 14 every 3 weeks. "We
started at a lower dose of
capecitabine than in some
other studies," Dr. Wardley said.
Patients in the two-drug arm
with disease progression were given the option to cross over to receive capecitabine.
The primary endpoint of the
study was overall response rate (ORR),
which includes complete response, partial
response, and stable disease.

Study Results
During a median follow-up of about
18 months, the researchers saw an overall
response rate of 71% in the tripledrug
arm, compared with 73% in the
two-drug arm, a nonsignificant difference.
"The ORRs in both arms are excellent,"
Dr. Wardley commented. "It
really shows that trastuzumab and
docetaxel and also these drugs with
capecitabine are good combinations for
this patient group."

The percentage of patients achieving
a complete response was 18% in the
three-drug combination arm and 15%
in the two-drug arm. "That's also very
good," Dr. Wardley said. "That might
be something worth looking at in patients
with earlier stages of breast cancer
because you may be able to eliminate
disease in some patients."

Median time to progression (time
from randomization until tumor growth)
showed a significant benefit of adding
capecitabine to the two-drug regimen.
In the three-drug arm, time to progression
was 18.2 months, compared with
13.8 months in the two-drug arm
(P = .045). "The improvement in time to
progression with capecitabine is interesting,"
Dr. Wardley said. "It's about 4.5
months, which in other studies has been
shown to be an important result."

There was also a trend toward an increase
in progression-free survival (time
from randomization to tumor growth or
death) with the three-drug combination,
from a median of 12.8 months to 14.8
months (P = .06).

No unexpected safety concerns were
noted by the external Data Safety Monitoring
Board, and the incidence of cardiac
failure was low (one patient in each
treatment arm), Dr. Wardley said.